A forced-circulation falling film evaporator (often abbreviated to FFE), a continuous concentrator that has generally been used in various chemical processes, comprises a shell-and-tube exchanger, a gas-liquid separator, a returning line, a circulation pump, a draw-out line, a condenser, and a taking-out line. The shell-and-tube exchanger, which is a heater, heats a liquid with a heating medium that has been heated to a temperature above the boiling point of the liquid under the operation pressure. The heating changes the liquid to a mixture of vapor and liquid. The gas-liquid separator divides the mixture into a gas phase comprising the vapor and a liquid phase. The separated liquid together with the feedstock is returned to the shell-and-tube exchanger through the returning line. The circulation pump is placed in this returning line through which the pump forcibly circulates the liquid. Part of the liquid separated with the gas-liquid separator is drawn out as a concentrated liquid through the draw-out line. The divided vapor is condensed in a condenser to a condensate, which is then taken out from the system through the taking-out line.
This continuous concentrator is operated so that the level of liquid in the gas-liquid separator is kept constant by controlling the amount of evaporating vapor through the adjustment of heating in the heater, while the ratio of the flow rate of the feedstock fed into the continuous concentrator to the flow rate of the concentrate withdrawn through the draw-out line is being kept constant. Alternatively, the concentrator is operated so that the level of liquid in the gas-liquid separator is kept constant by controlling the flow rate of the concentrate drawn from the gas-liquid separator through the returning line, while the ratio of the flow rate of the feedstock fed into the continuous concentrator to the amount of vapor produced in the heater through the control of heating is kept constant through adjustment of the heating.
In these days has been accelerated the application of separating technique with a large-scale chromatographic system to the production of important drugs or medicinal intermediates. As a method of effectively resolving a mixture of optical isomers, a simulated moving bed separation method, which is a continuous chromatographic method capable of continuous mass production, is prevailing. Optical resolution of a mixture of optical isomers utilizing this simulated moving bed separation method typically comprises optically resolving a feedstock by the method to obtain a dilute solution including the intended component; concentrating the dilute solution with a film heater to make a concentrate; and taking out the intended component in the form of powder or crystal by crystallization while recycling the solvent recovered by vaporization and condensation with a condenser. Because such mixtures of optical isomers are often vulnerable to heat, film heaters such as falling film evaporators (FFE) and wiped film evaporators (WFE) are commonly employed for the heater. The film heater has good heat transfer efficiency and small pressure loss, and therefore is suitable for operation under a reduced pressure. It is also capable of keeping low the temperature of the heating source.
Because drugs and medicinal intermediated are extremely expensive, strict shop floor control based on GMT is required in the manufacture of drugs and medicinal intermediates utilizing simulated moving bed separation methods.
This strict shop floor control is also applied to the crystallization step. Specifically, when the concentration of a solution fed to the crystallization step is too small, it may result in a poor crystallization of the intended component. Note that a solvent used for chromatography is usually a good solvent to the intended component; in other words, such a solvent has properties of hindering the crystallization. On the other hand, when the concentration of the solution is too large, crystallization may take place while the solution is being transferred to the crystallization step, or the solution may not be sent smoothly due to a high viscosity of the solution.
In a combined system of a forced-circulation falling film evaporator with a simulated moving bed separation apparatus, when the producing process starts, the initial concentration of the concentrate obtained through the process in the evaporator is small. Therefore, when a method for producing an expensive substance for drugs and important medicinal intermediates using the system is carried out, if the amount of the concentrate to be drawn out to the amount of the feedstock being fed to the concentrator is simply set, the concentration of the intended component in the concentrate withdrawn through the draw-out line is small until the continuous concentrator is operated in a stationary state. As a result, crystallization cannot be carried out effectively.
Besides, when operating conditions of the simulated moving bed separation apparatus are changed, adjusting the operating condition of the continuous concentrator cannot follow the changes quickly.